1. Field of the Invention
This invention relates to a novel method for the prophylaxis and treatment of symptoms associated with certain allergic reactions, such as, allergic extrinsic asthma and allergic rhinitis.
2. Description of the Prior Art
Current drug treatment of allergic asthma includes .beta.-adrenergic catecholamines, methylxanthines and, in severe cases, corticosteroids. However, such drugs have a broad spectrum of pharmacological activities, including effects other than anti-asthmatic effects, which limit their usefulness in asthma therapy. Thus there is a need for specific anti-asthmatic drugs. Such specific anti-asthmatic drugs would either antagonize the mediators of allergic bronchoconstriction e.g., histamine and SRS-A (slow reacting substance of anaphylaxis), or block the release of these mediators of allergic bronchoconstriction. An example of a specific anti-asthma drug that blocks the release of mediators of allergic reactions is disodium cromoglycate [Intal.RTM.; The Merck Index, Ninth Edition (1976), 2585], which has been found to be useful mainly against allergic asthma.
In addition to drugs which block the release of mediators of anaphylaxis, a second type of specific anti-asthmatic drug would antagonize the mediators of allergic bronchoconstriction rather than block their release. Histamine is one well documented mediator of allergic bronchospasm in man, but antihistamines are notably ineffective against asthmatic attacks. This is believed to be attributable to the relatively small amount of histamine released as a result of reagenic antibody-antigen interaction compared to the amount of SRS-A released. SRS-A, which has a profound constrictor effect and long duration of action, is a well documented mediator of anaphylaxis in man [K. F. Austen, Fed. Proc. 33;2256-2262 (1974); H. M. Guirgis and R. G. Townley, J. Allergy 53:74 (1974); P. J. Piper and J. L. Walker, Br. J. Pharmac. 47:291-304 (1973)], monkeys and guinea pigs [D. J. Stechschulte, R. P. Orange and K. F. Austen, J. Immunol. 111:1585-1589 (1973); R. Liebig, B. Peskar and Bernauer, Arch. Pharmacol. 282 Suppl.: R-58 (1974)]; and calves [J. F. Burka and P. Eyre, Can. J. Physiol. Pharmacol. 52:1201-1204 (1974)]. U.S. Pat. 3,882,148 describes a class of compounds which are indicated to be antagonists of SRS-A and thus useful in the treatment of disorders in which SRS-A is a factor, for example asthma, hay fever and skin afflictions. Antagonism of SRS-A also has been reported for other compounds [J. Med. Chem. 20:371-379 (1977); Nature New Biol. 245:215-217 (1973)].